Alessandro Follador

Drug waste minimisation and cost-containment in Medical Oncology: two-year results of a feasibility study.

BackgroundCost-containment strategies are required to face the challenge of rising drug expenditures in Oncology. Drug wastage leads to economic loss, but little is known about the size of the problem in this field.MethodsStarting January 2005 we introduced a day-to-day monitoring of drug wastage and an accurate assessment of its costs. An internal protocol for waste minimisation was developed, consisting of four corrective measures: 1. A rational, per pathology distribution of chemotherapy sessions over the week. 2. The use of multi-dose vials. 3. A reasonable rounding of drug dosages. 4. The selection of the most convenient vial size, depending on drug unit pricing.ResultsBaseline analysis focused on 29 drugs over one year. Considering their unit price and waste amount, a major impact on expense was found to be attributable to six drugs: cetuximab, docetaxel, gemcitabine, oxaliplatin, pemetrexed and trastuzumab. The economic loss due to their waste equaled 4.8% of the annual drug expenditure. After the study protocol was started, the expense due to unused drugs showed a meaningful 45% reduction throughout 2006.ConclusionOur experience confirms the economic relevance of waste minimisation and may represent a feasible model in addressing this issue.A centralised unit of drug processing, the availability of a computerised physician order entry system and an active involvement of the staff play a key role in allowing waste reduction and a consequent, substantial cost-saving.

Targeting the VEGF pathway: Antiangiogenic strategies in the treatment of non-small cell lung cancer

The management of advanced non-small cell lung cancer (NSCLC) has evolved considerably in recent years, due to a progressive understanding of tumour biology and the identification of promising molecular targets. Several agents have been developed so far inhibiting vascular endothelial growth factor (VEGF) - a key protein in tumour neoangiogenesis, growth and dissemination - or its receptor signalling system. The finding in study E4599 of a survival benefit for carboplatin-paclitaxel plus bevacizumab - a humanised anti-VEGF monoclonal antibody - over chemotherapy (CT) alone led the U.S. Food and Drug Administration (FDA) to approve the novel combination for first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC. In a randomised phase III trial presented at the American Society of Clinical Oncology (ASCO) 2007 Annual Meeting, patients receiving cisplatin-gemcitabine plus bevacizumab experienced a significantly longer progression-free survival (PFS) compared to the standard arm. Based on these data, the European Medicines Agency (EMEA) has granted marketing authorisation for bevacizumab in addition to any platinum-based CT for first-line treatment of advanced NSCLC other than predominantly squamous histology. Aim of this report is to provide an overview on bevacizumab in NSCLC, with special emphasis on clinical results presented at ASCO last meeting. Multitargeted tyrosine kinase inhibitors (TKIs), sharing a focus on both the angiogenesis process and additional cell-surface receptors, and VEGF Trap, a novel fusion protein with markedly higher affinity for VEGF than bevacizumab, will be briefly discussed as well.

Drug waste minimization as an effective strategy of cost-containment in Oncology

BackgroundSustainability of cancer care is a crucial issue for health care systems worldwide, even more during a time of economic recession. Low-cost measures are highly desirable to contain and reduce expenditures without impairing the quality of care. In this paper we aim to demonstrate the efficacy of drug waste minimization in reducing drug-related costs and its importance as a structural measure in health care management.MethodsWe first recorded intravenous cancer drugs prescription and amount of drug waste at the Oncology Department of Udine, Italy. Than we developed and applied a protocol for drug waste minimization based on per-pathology/per-drug scheduling of chemotherapies and pre-planned rounding of dosages.ResultsBefore the protocol, drug wastage accounted for 8,3% of the Department annual drug expenditure. Over 70% of these costs were attributable to six drugs (cetuximab, docetaxel, gemcitabine, oxaliplatin, pemetrexed and trastuzumab) that we named ‘hot drugs’. Since the protocol introduction, we observed a 45% reduction in the drug waste expenditure. This benefit was confirmed in the following years and drug waste minimazion was able to limit the impact of new pricely drugs on the Department expenditures.ConclusionsFacing current budgetary constraints, the application of a drug waste minimization model is effective in drug cost containment and may produce durable benefits.

Dramatic tumour response to pemetrexed single-agent in an elderly patient with malignant peritoneal mesothelioma: a case report

BackgroundTo date, there is no standard treatment for unresectable malignant peritoneal mesothelioma; either best supportive care or systemic chemotherapy with palliative intent are accepted options.Case presentationHere, we report the case of a 79-year old patient with malignant peritoneal mesothelioma who was treated with pemetrexed single-agent and obtained an impressive long-lasting response.ConclusionSingle-agent pemetrexed is a treatment option for malignant peritoneal mesothelioma in selected elderly patients or in patients with unpaired performance status.

Italian Survey on adjuvant treatment of non-small cell lung cancer (ISA)☆

BACKGROUND A recent pooled analysis of randomized trials indicated significant improvement in overall survival from cisplatin-based adjuvant chemotherapy for non-small cell lung cancer (NSCLC), depending on disease stage (only in stages II and III) and PS (≤ 1). Post-operative radiotherapy (RT) is optional for pN2 tumours. PATIENTS AND METHODS To evaluate opinions and daily clinical practice of Italian Oncologists about adjuvant treatment of NSCLC, a 46-item questionnaire was delivered via e-mail. RESULTS Seventy-eight physicians from 68 Centers (out of 98 contacted) returned their questionnaire. Seventy-four, 86, 94, and 78% of them give the indication for adjuvant chemotherapy for stage IIA, IIB, IIIA, and IIIB disease, respectively and 14% in stage IB disease. Stage, PS, and age are taken into consideration evaluating adjuvant approach by 97, 95 and 73%, respectively. Cisplatin-vinorelbine (64%) and cisplatin-gemcitabine (33%), for 4 cycles (81%), are the preferred regimens, while 32% use different regimens. Ninety-two percent indicate RT in pN2 disease and/or positive resection margins. Real Number of patients Needed to Treat (NNT) is probably not completely known/understood and/or used by physicians. CONCLUSIONS A substantial adherence between clinical daily practice in Italy and scientific progresses is described in this paper, even with some discordances regarding the most appropriate adjuvant chemotherapy regimen.

Impact of low-dose computed tomography screening on lung cancer mortality among asbestos-exposed workers

Background We previously showed that low-dose computed tomography (LDCT) screening in asbestos-exposed workers is effective in detecting lung cancer (LC) at an early stage. Here, we evaluate whether LDCT screening could reduce mortality from LC in such a high-risk population. Methods Within a cohort of 2433 asbestos-exposed men enrolled in an Occupational Health surveillance programme, we compared mortality between the participants in the ATOM002 study (LDCT-P, N  =  926) and contemporary non-participants (LDCT-NP, N  =  1507). We estimated standardized mortality ratios for the LDCT-P and LDCT-NP populations using regional and national rates (SMR_FVG and SMR_ITA, respectively). We compared survival for all causes, all neoplasms, LC and malignant neoplasm of pleura (MNP) between LDCT-P and LDCT-NP using Cox proportional hazard models adjusted for age, smoking history, asbestos exposure level and comorbidities. Results A reduction in mortality from LC was observed in the LDCT-P group compared with regional and national figures (SMR_FVG  =  0.55, 95% confidence interval (CI) 0.24-1.09; SMR_ITA  =  0.51, 95% CI 0.22-1.01); this was not the case for the LDCT-NP group (SMR_FVG  =  2.07, 95% CI 1.53-2.73; SMR_ITA  =  1.98, 95% CI 1.47-2.61). A strong reduction in LC mortality was observed for the LDCT-P compared with the LDCT-NP [hazard ratio (HR)  =  0.41, 95% CI 0.17-0.96]. Mortality was also reduced for all causes (HR  =  0.61, 95% CI 0.44-0.84), but not for all neoplasms (HR  =  0.97, 95% CI 0.62-1.50) and MNP (HR  =  0.86, 95% CI 0.31-2.41) within the LDCT-P population. Conclusions In our cohort, participation in the LDCT screening study was associated with reduced mortality from LC. This finding supports the use of LDCT in surveillance programmes for asbestos-exposed workers.

Real-time tests of multiple genome alterations take the first steps into the clinic: a learning example.

Molecular characterization is increasingly changing clinical practice, in both diagnosis and treatment. BRAF is a proto-oncogene that is mutated in ~2%–4% of lung cancers, but the incidence rises to 40%–45% among papillary thyroid cancers. Furthermore, BRAF is a promising target in lung cancer treatment. The present case study covers both the challenges of molecular differential diagnosis and the perspectives opened by targeted therapy by discussing the history of a 78-year-old female affected by a papillary histotype carcinoma with BRAF mutation associated with both thyroid and lung localizations. A differential diagnosis was possible as a consequence of a multidisciplinary approach including an in-depth molecular characterization. Based on this molecular feature, the patient was successfully treated with the BRAF inhibitor dabrafenib after the failure of treatment with standard regimen. To the best of our knowledge, this is the first published case of non-small-cell lung cancer with metastasis to thyroid and with BRAF V600E mutation.

423PO6-METHYLGUANINE-DNA METHYLTRANSFERASE (MGMT) CUT-OFF METHYLATION LEVEL DETERMINED BY PYROSEQUENCING AND CLINICAL OUTCOME IN PATIENTS WITH GLIOBLASTOMA MULTIFORME (GBM): A SINGLE-INSTITUTION EXPERIENCE

ABSTRACT Aim: MGMT gene is epigenetically silenced by its promoter hypermethylation in GBM. Hypermethylation is relevant predictor of response to temozolomide. Yet, there is debate around the best technique for MGMT assessment. One of the most interesting methods is pyrosequencing (PyroS) that allows defining a cut-off value for MGMT methylation Aim of our retrospective analysis was to explore if predefined levels of MGMT methylation could impact on overall survival (OS) in a cohort of GBM patients. We also analyzed the potential prognostic role of isocitrate dehydrogenase-1 (IDH1) by PyroS. Methods: Clinical and pathological data of 108 consecutive GBM patients referred to our Department between January 2008 and December 2013 were retrieved. Three groups of patients were identified: unmethylated with MGMT methylation 29% (HM). We calculated median (m) OS and compared the Kaplan Mayer survival curves across the groups through log rank test. Results: 51 cases (47.2%) were UM, 24 (22.2%) IM and 33 (30.6%) HM. The median follow-up is 38.5 months. mOS, months (95%CI) N 108 mOS, months (95%CI) Standard Stupp regimen, N 66 MGMT methylation 13.2 (8.3-15.2) 15.1 (12.8-17.4) MGMT methylation 9-29% 15.8 (9.8-30.8) 25.9 (6.93-53.5) MGMT methylation >29% 19.5 (11.5-47.1) 47 (18.5-57.6) P = 0.0002 P = 0.0001 mOS of IDH1 mutated patients (11 out of 108) was 53.5 months compared to 14.2 months in those wild type (p = 0.01). Conclusions: Our study confirms that a cut-off level of 9% in MGMT methylation has prognostic and predictive value in GBM patients treated with standard therapy. IDH1 mutation may have a prognostic role, although the small patient number does not allow drawing definitive conclusions. Disclosure: All authors have declared no conflicts of interest.

Fulminating septic shock from Clostridium perfringens in an early breast cancer patient with severe myalgia after docetaxel treatment

Anaerobic bacteraemia could be a life-threatening condition in neutropenic patients receiving chemotherapy. Taxane therapy is associated with necrotising inflammation of the caecum (named also typhlitis) that could be a potential source for bacteraemia. We report the case of a sudden onset of septic shock by Clostridium perfringens in a young patient treated with docetaxel as adjuvant chemotherapy for early breast cancer. A mini-review of the literature has been performed.

Lung cancer and mesothelioma screening with low-dose spiral computed tomography (LDCT) in 1,000 asbestos-exposed workers: An Alpe-Adria Thoracic Oncology Multidisciplinary group study (ATOM 002)

7048 Background: LDCT is more sensitive than chest radiography (CXR) for detection of early stage lung cancer in heavy smokers. However, little is known about LDCT screening in asbestos-exposed subjects. To address this issue, we have designed a prospective, nonrandomized trial to evaluate baseline and annual repeat screening with LDCT in 1,000 asymptomatic asbestos-exposed workers. Here, we report the results of the baseline screening. METHODS Eligibility criteria include: exposure to asbestos, age 40 to 75 yrs, no prior cancer or severe concomitant conditions, no chest CT scan in the last 2 yrs. After written informed consent, eligible subjects undergo a structured interview, CXR and LDCT. Subjects with negative baseline exams undergo annual repeat LDCT. Subjects with positive baseline exams undergo high resolution CT (HRCT) and additional diagnostic workup. RESULTS Between February 2002 and October 2003, 1007 volunteers have been enrolled. Subject characteristics: median age, 59 yrs; males, 97%; smoking history, 66%; former or current shipyard workers, 78%; median asbestos exposure time, 30 yrs. The following data refer to 943 participants. On LDCT, 619 non calcified nodules (NCN) have been identified in 41% of participants. CXR detected 43 nodules. Pleural abnormalities have been detected in 42% and 69% of participants by CXR and LDCT, respectively. So far, six cases of stage I lung cancer have been diagnosed and treated with radical surgery: 3 bronchioloalveolar carcinomas, 1 carcinosarcoma, 2 adenocarcinomas. In addition, one malignant pleural mesothelioma and one thymic carcinoid have been identified. CONCLUSIONS LDCT seems to be useful for the early detection of lung cancer also in asbestos-exposed subjects. Annual repeat LDCT screening may provide information on the natural history and evolution of asbestos-related pleural abnormalities. Study supported by Compagnia di San Paolo, Torino, and Provincia di Gorizia. No significant financial relationships to disclose.